Andrew Miri

Northwestern University
2019 Scholar

Research Interests

The Neural Basis of Motor Skills on the Timescale of Movement 

The patterns of muscle activation that drive mammalian movement reflect an interplay between networks of neurons in the spinal cord and neurons in an array of brain regions that comprise the motor system. However, current models of motor system operation say little about this interplay on the short timescales over which neurons communicate and movement unfolds. Our research combines novel genetically-mediated approaches for measuring and perturbing activity in neuronal subpopulations with quantitative and model-based analyses to understand this interplay. Here are some examples of our current interests:

Skilled movement generation in real time – Motor skills are movements that animals improve with repeated practice. The capacity to improve motor behaviors is vital to the fitness these behaviors confer, and so to the evolutionary success of many mammalian species.  Many motor system regions appear critical for driving motor skills, but it is unclear how these regions interact in real time to ensure such movements are properly orchestrated. Our approach is behavior-centric, exploring how neuronal populations within motor system regions conspire to execute a model skilled movement. We assess interactions between neuronal populations by combining rapid activity perturbations via optogenetic probes with large-scale electrical and optical activity measurement in one or more populations as movements are executed.

Understanding the cortical orchestration of movement – Motor areas of the brain’s neocortex play a particular role in facilitating the remarkable complexity and agility of mammalian movement, but we understand little about how. In contrast to previous approaches that have assessed cortical function with respect to movement type, we focus on how motor cortical influence depends on the underlying muscle activation patterns themselves, which we quantify via EMG. Our recent findings suggest that there are certain components of motor cortical output activity that directly drive muscles, while other components may serve other roles. Coupling activity measurement and perturbation here allows us to further investigate this sort of functional discretization among motor cortical output components.

Identifying the functional units of corticospinal control – The resolution of subatomic particles or of DNA structure illustrate how mechanistic insight can rapidly mount after the appropriate functional units for explaining a given phenomenon are identified. However for many neural processes, the appropriate functional units for describing the underlying mechanism remain unclear. We aim to characterize the relationship between neuronal identity and function within the corticospinal population by combining two-photon imaging of neural activity in mice performing skilled forelimb movements together with genetic access to subtypes defined by transcriptomic state, projection patterns, and postsynaptic partner identity. By resolving how corticospinal neuron features align with function, light will be shed on the appropriate functional elements with which to describe motor system operation.

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